Publication Details

Category Text Publication
Reference Category Journals
DOI 10.1021/bi0521543
Title (Primary) Global hairpin folding of tau in solution
Author Jeganathan, S.; von Bergen, M.; Brutlach, H.; Steinhoff, H.J.; Mandelkow, E.
Source Titel Biochemistry
Year 2006
Department PROTEOM
Volume 45
Issue 7
Page From 2283
Page To 2293
Language englisch
Abstract The microtubule-associated protein tau stabilizes microtubules in its physiological role, whereas it forms insoluble aggregates (paired helical filaments) in Alzheimer's disease. Soluble tau is considered a natively unfolded protein whose residual folding and intramolecular interactions are largely undetermined. In this study, we have applied fluorescence resonance energy transfer (FRET) and electron paramagnetic resonance (EPR) to examine the proximity and flexibility of tau domains and the global folding. FRET pairs spanning the tau molecule were created by inserting tryptophans (donor) and cysteines (labeled with IAEDANS as an acceptor) by site-directed mutagenesis. The observed FRET distances were significantly different from those expected for a random coil. Notably, the C-terminal end of tau folds over into the vicinity of the microtubule-binding repeat domain, the N-terminus remains outside the FRET distance of the repeat domain, yet both ends of the molecule approach one another. The interactions between the domains were obliterated by denaturation in GdnHCl. Paramagnetic spin-labels attached in various domains of tau were analyzed by EPR and exhibited a high mobility throughout. The data indicate that tau retains some global folding even in its "natively unfolded" state, combined with the high flexibility of the chain.
Persistent UFZ Identifier
Jeganathan, S., von Bergen, M., Brutlach, H., Steinhoff, H.J., Mandelkow, E. (2006):
Global hairpin folding of tau in solution
Biochemistry 45 (7), 2283 - 2293 10.1021/bi0521543